Doctors from Great Ormond Street Hospital, in Londres, applied an innovative treatment to 11 patients with refractory T-cell acute lymphoblastic leukemia. The therapy, developed by University College London, uses base editing to modify donor T cells and transform them into specific cancer fighters. Realizado Since 2022, the procedure has achieved remission in nine cases, allowing subsequent bone marrow transplants.
Seven patients, including children and adults, remain undetected after periods of three months to three years. The method involves infusion of the modified cells, followed by chemotherapy to eliminate the old immune system. Essa approach appears as an option for cases where chemotherapy and transplants have failed, offering the prospect of a cure for leukemias considered terminal.
T-cell acute lymphoblastic leukemia represents about 25% of pediatric acute leukemia cases and mainly affects young people. Antes of treatment, options were limited to palliative care, with a prognosis of months. Agora, the study published in New England Journal of Medicine highlights the precision of gene editing, which changes a single base in cells’ DNA.
- Main stages of therapy: collection of healthy T cells from a donor;
- Genetic editing to disable self-attack mechanisms;
- Insertion of instructions for targeting cancer cells;
- Infusion and post-treatment monitoring.
Base editing mechanism of action
Base editing technology precisely alters the genetic code of T cells, converting them into a “living medicine”. Esse process deactivates the CD7 receptor on therapeutic cells, preventing their destruction by the body itself, while directing the attack against leukemia cells that express the marker.
Patients receive the infusion in a hospital environment, with intensive monitoring for infections due to temporary immune suppression. Após four weeks, if the cancer is not detected, a bone marrow transplant continues to rebuild the defense system.
The procedure takes hours in the infusion, but the genetic preparation takes weeks in the laboratory. In two cases, the disease reappeared because the cancer cells lost the CD7 marker, escaping targeting, which reinforces the need for future adaptations.
Initial results show that the modified cells persist in the body, offering prolonged protection against relapses. Essa persistence differentiates the therapy from conventional treatments, which often require repetitions.
Success stories in young patients
Alyssa Tapley, 16 years of Leicester, became the first global patient treated in 2022 at Great Ormond Street Hospital. Diagnosticada with incurable leukemia after failed chemotherapy and transplants, she now presents annual negative tests for the disease and plans studies in biomedicine.
Another eight pediatric cases and two adults, all with poor prognoses, achieved deep remission. An adult patient, aged 45, reported returning to daily activities three months after treatment, with no signs of recurrence on imaging and blood tests.
These results occur in a context of high lethality: refractory T leukemia has a survival rate below 10% with standard therapies. Adapted CAR-T therapy raises this mark to 64% in early remission.
Ongoing monitoring includes monthly testing for the first six months, with gradual tapering. Nenhum patient reported serious side effects beyond expected immune suppression, managed with prophylactic antibiotics.
Risks and post-infusion monitoring
Challenges in Global Therapy Implementation
The treatment requires specialized centers with gene editing laboratories, limiting its initial access to institutions like Great Ormond Street. No Brasil, similar studies are progressing in Hemocentro and Ribeirão Preto, in partnership with USP and Butantan, aiming for local production to reduce costs by up to 80%.
These efforts include 81-patient phase 1/2 trials for B lymphoblastic leukemia, scheduled for completion in 2026. Anvisa has approved protocols for domestic manufacturing, focusing on refractory patients after two lines of treatment.
International partnerships, such as with Hospital Clínic of Barcelona, explore low-toxicity versions, with 90% response rates in acute leukemia. Esses agreements aim to transfer technology to the SUS, expanding the reach.
National production faces logistical barriers, such as the cold chain for living cells, but tests on 20 compassionate patients already demonstrate feasibility. Expectativa is to register the therapy with Anvisa in 2026, integrating it into the public system.
Prospects for expansion into other cancers
Initiatives at Einstein Hospital Israelita test CAR-T against CD19 for leukemias and lymphomas, with 40 patients treated so far. Esses studies include NK cells for acute myeloid leukemia, expanding the scope beyond the T variant.
In the Brazilian context, Ministério of Saúde invests R$542 million in cell therapy platforms, including Fiocruz for oncology and genetics. Isso positions the country as a regional hub, focusing on accessibility for diffuse lymphoma and multiple myeloma.
Advances in viral vectors improve the efficiency of genetic modification, reducing production time from weeks to days. Ensaios in solid tumors such as neuroblastoma show durable remission over 18 years in pediatric cases.
Integration with genomic sequencing allows customization, identifying specific mutations for precise targeting. Esses developments promise to increase cure rates in refractory hematological cancers globally.
Initial applications in Brasil and partnerships
Hemocentro of Ribeirão Preto began phase 2 of the CARTHEDRALL study in January 2025, recruiting at centers such as HC-FMUSP and Sírio Libanês. The protocol treats 81 volunteers with refractory B leukemia, evaluating safety and response in 30 days.
Preliminary results indicate remission in 60% of initial cases, comparable to imported therapies. Local production uses GMP standards, ensuring quality for scaling.
Collaborations with US-based Caring Cross improve allogeneic versions, using universal multi-patient donors. Isso reduces costs from R$3 million to around R$100 thousand, enabling inclusion in the SUS.
Monitoring includes neurotoxicity and cytokine release syndrome, common in 20% of cases but manageable with standardized protocols. Avanços these reduce incidence to less than 10%.
Future of immunotherapy in hematologic oncology
Base editing therapy represents a leap beyond conventional CAR-T, with a lower risk of antigen escape. Estudos in AML explore targets such as CLL-1, with remissions in 42-100% of refractory cases, as per 2024 reviews.
In Brasil, CCTA coordinates allogeneic development, with Fapesp and Embrapii, for 80 volunteers in B lymphoma. Esses efforts integrate AI for response prediction, optimizing patient selection.
Overall, New England Journal of Medicine reports cellular persistence for 10 years, controlling relapses. Isso establishes immunotherapy as a pillar in guidelines, alongside chemotherapy.
Challenges persist in elderly people with comorbidities, where toxicity requires adjustments, but combinations with venetoclax increase efficacy by 67% for CML. Focus on accessibility drives research for solid tumors.
